Mutation for Hereditary Atrial Fibrillation Identified

Researchers have found that a rare inherited form of atrial fibrillation (AF) is caused by a mutation in the KCNQ1 gene that encodes an ion channel subunit protein. Their finding was published in the January 10, 2003, issue of Science.

Nearly one out of every 20 individuals over age 65 suffers from cardiac arrhythmia, which is increasing in prevalence as the population ages. Untreated AF can lead to heart muscle dysfunction, embolism, ventricular arrhythmia, and heart failure. Investigators studied a four-generation family in China with a history of AF. Of the 44 living members of this family from rural villages, 16 have cases of AF, all of which the researchers confirmed were hereditary. Gene mapping studies led the researchers to a region of chromosome 11 that was linked to AF. Sequence analysis revealed that there was a specific nucleotide substitution in the KCNQ1 gene in all of the family members affected with AF, but not in unaffected family members. Cell culture analyses confirmed that this genetic alteration disrupted the function of the KCNQ1 potassium channel.

The KCNQ1 potassium channel, like other ion channels, controls the electrical activity of the heart in excitable heart cells, or myocytes. "The mutation in KCNQ1 causes a marked enhancement of its function, tips the normal balance of the process, and renders the cardiac myocytes more susceptible to atrial fibrillation, explained lead authors Dr. Yi-Han Chen of Tongji University (Shanghai, China) and Dr. Shi-Jie Xu of the Chinese National Human Genome Center (Shanghai, China). "This new understanding of the molecular basis of atrial fibrillation may lead to better pre-symptomatic diagnosis of the disorder and to the development of new therapies.”


Related Links:
Tongji University
Chinese National Human Genome Center